Recommended Citation
Turner T, Tuifua T, MacDonald W. Multimodality Imaging in MSH6-Associated Lynch Syndrome: Radiologic Contributions to Early Detection and Management of Recurrent GI Malignancy. Presented at Scientific Day; May 20, 2026; Milwaukee, WI.
Abstract
Background/Significance:
Lynch syndrome, caused by pathogenic variants in DNA mismatch repair (MMR) genes, increases risk for colorectal, small-bowel, and periampullary cancers. In MSH6-associated disease, tumors may appear proficient on immunohistochemistry (pMMR) despite underlying germline dysfunction, complicating surveillance. Because lesions often arise beyond routine endoscopic reach, cross-sectional imaging plays a critical role in early detection and treatment planning.
Description:
Patient with Lynch syndrome (germline MSH6 c.3694del3, likely pathogenic, and an additional MSH6 p.S998F variant of uncertain significance in trans) developed invasive colon adenocarcinoma at age 38 with pMMR by immunohistochemistry. Years later, endoscopy suggested a duodenal lesion with high-grade dysplasia; contrast-enhanced computed tomography (CT) and magnetic resonance enterography (MRE) clarified lesion extent, transmural invasion, and lack of nodal disease, guiding resection of a poorly differentiated adenocarcinoma (pT3N0). A subsequent periampullary recurrence was localized using pancreas-protocol multiphase CT, targeted esophagogastroduodenoscopy (EGD), and capsule endoscopy. Biopsy demonstrated invasive adenocarcinoma with deficient MMR (dMMR) due to loss of MSH6 expression. Given close margins and the morbidity of pancreaticoduodenectomy, the multidisciplinary team pursued programmed cell death-1 (PD-1) inhibitor therapy (pembrolizumab) for one year. Serial CT, MRE, and capsule endoscopy showed no radiologic evidence of recurrence on follow-up.
Discussion:
This case highlights the importance of multimodality imaging in MSH6-associated Lynch syndrome, where malignancies may be subtle, multifocal, or obscured by postoperative anatomy. Teaching points include: Combined MRE, multiphase CT, and capsule endoscopy to evaluate the proximal small bowel and periampullary region; Use of cross-sectional imaging to distinguish recurrence from postsurgical change; Low threshold for advanced imaging when discordant MMR results or equivocal endoscopic findings are present. These findings support incorporating scheduled cross-sectional imaging into surveillance for MSH6 carriers when endoscopy is negative or indeterminate. Multimodality imaging directly influenced diagnosis, staging, and management in this patient with MSH6-associated Lynch syndrome and recurrent gastrointestinal malignancy. Radiologic surveillance is essential for early detection and informed treatment decisions in this high-risk population.
Presentation Notes
Presented at Scientific Day; May 20, 2026; Milwaukee, WI.
Full Text of Presentation
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Document Type
Poster
Open Access
Available to all.
Multimodality Imaging in MSH6-Associated Lynch Syndrome: Radiologic Contributions to Early Detection and Management of Recurrent GI Malignancy
Background/Significance:
Lynch syndrome, caused by pathogenic variants in DNA mismatch repair (MMR) genes, increases risk for colorectal, small-bowel, and periampullary cancers. In MSH6-associated disease, tumors may appear proficient on immunohistochemistry (pMMR) despite underlying germline dysfunction, complicating surveillance. Because lesions often arise beyond routine endoscopic reach, cross-sectional imaging plays a critical role in early detection and treatment planning.
Description:
Patient with Lynch syndrome (germline MSH6 c.3694del3, likely pathogenic, and an additional MSH6 p.S998F variant of uncertain significance in trans) developed invasive colon adenocarcinoma at age 38 with pMMR by immunohistochemistry. Years later, endoscopy suggested a duodenal lesion with high-grade dysplasia; contrast-enhanced computed tomography (CT) and magnetic resonance enterography (MRE) clarified lesion extent, transmural invasion, and lack of nodal disease, guiding resection of a poorly differentiated adenocarcinoma (pT3N0). A subsequent periampullary recurrence was localized using pancreas-protocol multiphase CT, targeted esophagogastroduodenoscopy (EGD), and capsule endoscopy. Biopsy demonstrated invasive adenocarcinoma with deficient MMR (dMMR) due to loss of MSH6 expression. Given close margins and the morbidity of pancreaticoduodenectomy, the multidisciplinary team pursued programmed cell death-1 (PD-1) inhibitor therapy (pembrolizumab) for one year. Serial CT, MRE, and capsule endoscopy showed no radiologic evidence of recurrence on follow-up.
Discussion:
This case highlights the importance of multimodality imaging in MSH6-associated Lynch syndrome, where malignancies may be subtle, multifocal, or obscured by postoperative anatomy. Teaching points include: Combined MRE, multiphase CT, and capsule endoscopy to evaluate the proximal small bowel and periampullary region; Use of cross-sectional imaging to distinguish recurrence from postsurgical change; Low threshold for advanced imaging when discordant MMR results or equivocal endoscopic findings are present. These findings support incorporating scheduled cross-sectional imaging into surveillance for MSH6 carriers when endoscopy is negative or indeterminate. Multimodality imaging directly influenced diagnosis, staging, and management in this patient with MSH6-associated Lynch syndrome and recurrent gastrointestinal malignancy. Radiologic surveillance is essential for early detection and informed treatment decisions in this high-risk population.
Affiliations
Aurora St. Luke’s Medical Center